Furthermore, the majority (88%) of participants in the best supportive care only group later switched to pazopanib as a compassionate treatment and these patients achieved a median 3.5 months of PFS after pazopanib initiation, report Jean-Yves Blay, from Centre Léon Bérard in Lyon, France, and fellow PAZOGIST study group investigators.

“This trial provides reference outcome data for future studies of targeted inhibitors in the third-line setting for these patients”, they write in The Lancet Oncology.

Grade 3 or more severe adverse effects associated with pazopanib were reported by 72% of the 76 patients given the TKI in the two trial arms, including hypertension in 36–38%, and serious pazopanib-related events occurred in 17–35% of the patients, with eight patients developing pulmonary embolism. There were three pazopanib-related deaths (two cases of pulmonary embolism and one hepatic cytolysis).

“Tolerance of the treatment was consistent with the clinical experience gained in similar patient populations (with advanced sarcoma and advanced renal cell carcinoma)”, the authors observe.

Exploratory analysis indicated that PFS might be higher in patients who had not undergone gastrectomy. This and mutations in KIT and PDGFRA may account for the difference in outcome in a second recent trial of pazopanib for refractory GIST which was terminated early for poor PFS findings, Jean-Yves Blay et al hypothesise.

In an accompanying comment, Toshirou Nishida and Toshihiko Doi, from National Cancer Center Hospital East in Kashiwa, Japan, note it is unknown whether pazopanib has anti-tumour efficacy by inhibiting KIT and PDGFRα in GIST or by an antiangiogenesis effect through vascular endothelial growth factor inhibition.

“Because of the low proportion of patients achieving a response and limited efficacy despite the cost, it is important to ascertain pazopanib's mechanism of action and molecular markers to identify patients who will benefit from the drug”, they emphasize.